title: Antiproliferative property of hexadecyloxypropyl 9-[2-(phosphonomethoxy) ethyl] guanine (HDP-PMEG) for unwanted ocular proliferation.
abstract: OBJECTIVE
  To investigate the safety and inhibitory effects of hexadecyloxypropyl 9-[2-(phosphonomethoxy) ethyl] guanine (HDP-PMEG) on ocular cell proliferation and collagen matrix contraction.
  
  
  METHODS
  For the antiproliferation studies, various ocular cell monolayers were exposed to HDP-PMEG, PMEG, 5-fluorouracil (5-FU), and daunorubicin (DNB). For the collagen contraction studies, retinal pigment epithelium (RPE) cells seeded onto type I collagen lattices were exposed for a single 5- or 50-min period to various concentrations of HDP-PMEG or 5-FU. For the cytotoxicity study, trypan blue exclusion tests were performed using a human Müller cell line. Cytotoxicity was determined up to 4 days after treatment.
  
  
  RESULTS
  The proliferation of RPE cells, scleral fibroblasts, vessel endothelial cells, and ocular melanoma cells can all be significantly inhibited by HDP-PMEG. Its inhibitory effects on those cells were uniformly stronger than that of 5-FU. Contraction of the collagen matrix containing RPE cells was significantly inhibited by HDP-PMEG and by 5-FU at concentrations of 20 µM and 2,000 µM, respectively, as compared with controls (p<0.05). The safety profile of HDP-PMEG was significantly better than 5-FU and daunorubicin. The ocular therapeutic index is 1,100 for HDP-PMEG, 17.2 for 5-FU, and 1.25 for daunorubicin.
  
  
  CONCLUSIONS
  HDP-PMEG possesses a significant inhibitory effect on the proliferation of RPE, retinal glial cells, scleral fibroblasts, and ocular melanoma cells. HDP-PMEG is also genotoxic and may be used as a single short application for the modulation of unwanted ocular proliferation.
authors.affiliation: Institute of Ocular Pharmacology, School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang,China.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Hou
authors.forename: Yuli
authors.initials: Y
authors.lastname: Li
authors.forename: Zhonglou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Nadejda
authors.initials: N
authors.lastname: Valiaeva
authors.forename: James R
authors.initials: JR
authors.lastname: Beadle
authors.forename: Karl
authors.initials: K
authors.lastname: Hostetler
authors.forename: William R
authors.initials: WR
authors.lastname: Freeman
authors.forename: Dan-Ning
authors.initials: DN
authors.lastname: Hu
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Lingyun
authors.initials: L
authors.lastname: Cheng
mesh_terms: D001681:Biological Assay; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005123:Eye / Q000166:cytology*; D005472:Fluorouracil / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D009943:Organophosphorus Compounds; C063380:9-((2-phosphonylmethoxy)ethyl)guanine; D006147:Guanine; D003094:Collagen; D005472:Fluorouracil